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Spindle checkpoint


During the process of cell division, the spindle checkpoint prevents separation of the duplicated chromosomes until each chromosome is properly attached to the spindle apparatus. In order to preserve the cell's identity and proper function, it is necessary to maintain the appropriate number of chromosomes after each cell division. An error in generating daughter cells with fewer or greater number of chromosomes than expected (a situation termed aneuploidy), may lead in best case to cell death, or alternatively it may generate catastrophic phenotypic results. Examples include:

The mechanisms verifying that all the requirements to pass to the next phase in the cell cycle have been fulfilled are called checkpoints. All along the cell cycle, there are different checkpoints. The checkpoint ensuring that chromosome segregation is correct is termed spindle assembly checkpoint (SAC), spindle checkpoint or mitotic checkpoint. During mitosis or meiosis, the spindle checkpoint prevents anaphase onset until all chromosomes are properly attached to the spindle. To achieve proper segregation, the two on the sister chromatids must be attached to opposite spindle poles (bipolar orientation). Only this pattern of attachment will ensure that each daughter cell receives one copy of the chromosome.

When cells are ready to divide, because cell size is big enough or because they receive the appropriate stimulus, they activate the mechanism to enter into the cell cycle, and they duplicate most organelles during S (synthesis) phase, including their centrosome. Therefore, when the cell division process will end, each daughter cell will receive a complete set of organelles. At the same time, during S phase all cells must duplicate their DNA very precisely, a process termed DNA replication. Once DNA replication has finished, in eukaryotes the DNA molecule is compacted and condensed, to form the mitotic chromosomes, each one constituted by two sister chromatids, which stay held together by the establishment of cohesion between them; each chromatid is a complete DNA molecule, attached via microtubules to one of the two centrosomes of the dividing cell, located at opposed poles of the cell. The structure formed by the centrosomes and the microtubules is named mitotic spindle, due to its characteristic shape, holding the chromosomes between the two centrosomes. Both sister chromatids stay together until anaphase; at this moment they separate from each other and they travel towards the centrosome to which they are attached. In this way, when the two daughter cells separate at the end of the division process, each one will receive a complete set of chromatids. The mechanism responsible for the correct distribution of sister chromatids during cell division is named chromosome segregation.


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